Table 1.
Gene–drug pairs with high and moderate (Group 1 and 2) evidence of association as graded by PharmGKB.
| Evidence Level | Drug | Gene | Allele/Variant | AFR | EAS | EUR | Effect | Total Articles | Pediatric Articles | All ref. | Ped. ref. | Condition (Pediatric) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Level 1 | Thiopurines | TPMT | *2 rs1800462 | 0.001 | 0.000 | 0.006 | Dosage, Toxicity/ADR | 96 | 30 | [23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119] | [89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118] | Acute lymphoblastic leukemia |
| *3B rs1800460 | 0.003 | 0.000 | 0.028 | |||||||||
| *3C rs1142345 | 0.067 | 0.022 | 0.029 | |||||||||
| *4 rs1800584 | NA | NA | NA | |||||||||
| NUDT15 | *2 and *3 rs116855232 | 0.008 | 0.095 | 0.002 | Dosage, Toxicity/ADR | 9 | 6 | [120,121,122,123,124,125,126,127,128,129,130,131,132] | [120,121,122,123,124,125,126] | Acute lymphoblastic leukemia | ||
| Cisplatin | XPC | rs2228001 | 0.249 | 0.333 | 0.405 | Toxicity/ADR | 2 | 1 | [133,134] | [133] | Osteosarcoma | |
| Level 2 | Cisplatin | ERCC1 | rs3212986 rs11615 |
0.291 0.037 |
0.299 0.262 |
0.250 0.622 |
Efficacy, Toxicity/ADR | 11 | 0 | [135,136,137,138,139,140,141,142,143,144,145,146,147] | NS | |
| GSTM1 | Null | NA | NA | NA | Efficacy | 3 | 0 | [148,149,150] | NS | |||
| TP53 | rs1042522 | 0.669 | 0.414 | 0.285 | Efficacy, Toxicity/ADR | 5 | 0 | [139,140,151,152,153] | NS | |||
| XRCC1 | rs25487 | 0.110 | 0.235 | 0.366 | Toxicity/ADR | 9 | 0 | [136,137,138,139,140,154,155,156,157] | NS | |||
| Carboplatin | EGFR | rs121434568 | NA | NA | NA | Efficacy | 8 | 0 | [158,159,160,161,162,163,164,165] | NS | ||
| ERCC1 | rs11615 | 0.037 | 0.262 | 0.622 | Efficacy, Toxicity/ADR | 11 | 0 | [135,136,137,138,139,140,141,142,143,144,145,146,147] | NS | |||
| MTHFR | rs1801133 | 0.090 | 0.296 | 0.365 | Efficacy | 2 | 0 | [166,167] | NS | |||
| XRCC1 | rs25487 | 0.110 | 0.235 | 0.366 | Efficacy, Toxicity/ADR | 9 | 0 | [136,137,138,139,140,154,155,156,157] | NS | |||
| Methotrexate | ABCB1 | rs1045642 | 0.150 | 0.398 | 0.518 | Toxicity/ADR | 3 | 2 | [168,169,170] | [168,170] | Lymphoma | |
| ATIC | rs4673993 | 0.095 | 0.294 | 0.313 | Efficacy | 2 | 0 | [171,172] | NS | |||
| MTHFR | rs1801133 | 0.090 | 0.295 | 0.365 | Efficacy, Toxicity/ADR | 37 | 26 | [100,169,170,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206] | [100,170,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196] | Acute lymphoblastic leukemia | ||
| MTRR | rs1801394 | 0.246 | 0.263 | 0.523 | Toxicity/ADR, Metabolism/PK | 3 | 3 | [185,207,208] | [185,207,208] | Acute lymphoblastic leukemia | ||
| SLCO1B1 | rs11045879 | 0.189 | 0.453 | 0.190 | Toxicity/ADR | 4 | 3 | [209,210,211,212] | [209,210,211] | Acute lymphoblastic leukemia | ||
| Level 2 | Cyclophosphamide | GSTP1 | rs1695 | 0.480 | 0.179 | 0.331 | Efficacy, Toxicity/ADR | 2 | 0 | [213,214] | NS | |
| MTHFR | rs1801133 | 0.090 | 0.296 | 0.365 | Toxicity/ADR | 3 | 1 | [151,188,204] | [188] | Osteosarcoma | ||
| SOD2 | rs4880 | 0.424 | 0.125 | 0.466 | Efficacy | 1 | 0 | [215] | NS | |||
| TP53 | rs1042522 | 0.669 | 0.414 | 0.285 | Efficacy, Toxicity/ADR | 5 | 0 | [139,140,151,152,153] | NS | |||
| Irinotecan | C8orf34 | rs1517114 | 0.424 | 0.122 | 0.363 | Toxicity/ADR | 1 | 0 | [216] | NS | ||
| SEMA3C | rs7779029 | 0.365 | 0.152 | 0.047 | Toxicity/ADR | 1 | 0 | [216] | NS | |||
| UGT1A1 | rs8175347 rs4148323 |
NA 0.001 |
NA 0.138 |
NA 0.007 |
Toxicity/ADR | 35 | 1 | [217,218,219,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254] | [249] | Solid tumors |
Description of columns: 1: Evidence level; 2: drug name; 3: genes associated with drug; 4: genetic variant investigated; 5–7: Minor allele frequencies (MAF) were obtained from 1000 Genomes Consortium, Phase 3_V1-: AFR—African, EUR—European, EAS—East Asian; 8: Pharmacogenetic effect, 9: total number of articles; 10: number of pediatric articles; 11: references of total articles; 12: references of pediatric articles; 13: pediatric condition under investigation. NA—not available, NS—no study, PK—pharmacokinetic.